Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation

Age-related skeletal muscle sarcopenia is linked with increases in falls, fractures, and death and therefore has important socioeconomic consequences. The molecular mechanisms controlling age-related muscle loss in humans are not well understood, but are likely to involve multiple signaling pathways. This study investigated the regulation of several genes and proteins involved in the activation of key signaling pathways promoting muscle hypertrophy, including GH/STAT5, IGF-1/Akt/GSK-3&beta;/4E-BP1, and muscle atrophy, including TNF&alpha;/SOCS-3 and Akt/FKHR/atrogene, in muscle biopsies from 13 young (20 &plusmn; 0.2 years) and 16 older (70 &plusmn; 0.3 years) males. In the older males compared to the young subjects, muscle fiber cross-sectional area was reduced by 40&ndash;45% in the type II muscle fibers. TNF&alpha; and SOCS-3 were increased by 2.8 and 1.5 fold, respectively. Growth hormone receptor protein (GHR) and IGF-1 mRNA were decreased by 45%. Total Akt, but not phosphorylated Akt, was increased by 2.5 fold, which corresponded to a 30% reduction in the efficiency of Akt phosphorylation in the older subjects. Phosphorylated and total GSK-3&beta; were increased by 1.5 and 1.8 fold, respectively, while 4E-BP1 levels were not changed. Nuclear FKHR and FKHRL1 were decreased by 73 and 50%, respectively, with no changes in their atrophy target genes, atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated by 2 and 1.4 fold. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNF&alpha;, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation.<br /

Adaptation of eye and hand movements to target displacements of different size

Previous work has documented that the direction of eye and hand movements can be adaptively modified using the double-step paradigm. Here we report that both motor systems adapt not only to small direction steps (5° gaze angle) but also to large ones (28° gaze angle). However, the magnitude of adaptation did not increase with step size, and the relative magnitude of adaptation therefore decreased from 67% with small steps to 15% with large steps. This decreasing efficiency of adaptation may reflect the participation of directionally selective neural circuits in double-step adaptation

The rapid assembly of an elliptical galaxy of 400 billion solar masses at a redshift of 2.3

Stellar archeology shows that massive elliptical galaxies today formed rapidly about ten billion years ago with star formation rates above several hundreds solar masses per year (M_sun/yr). Their progenitors are likely the sub-millimeter-bright galaxies (SMGs) at redshifts (z) greater than 2. While SMGs' mean molecular gas mass of 5x10^10 M_sun can explain the formation of typical elliptical galaxies, it is inadequate to form ellipticals that already have stellar masses above 2x10^11 M_sun at z ~ 2. Here we report multi-wavelength high-resolution observations of a rare merger of two massive SMGs at z = 2.3. The system is currently forming stars at a tremendous rate of 2,000 M_sun/yr. With a star formation efficiency an order-of-magnitude greater than that of normal galaxies, it will quench the star formation by exhausting the gas reservoir in only ~200 million years. At a projected separation of 19 kiloparsecs, the two massive starbursts are about to merge and form a passive elliptical galaxy with a stellar mass of ~4x10^11 M_sun. Our observations show that gas-rich major galaxy mergers, concurrent with intense star formation, can form the most massive elliptical galaxies by z ~ 1.5.Comment: Appearing in Nature online on May 22 and in print on May 30. Submitted here is the accepted version (including the Supplementary Information), see nature.com for the final versio

Borrelia valaisiana resist complement-mediated killing independently of the recruitment of immune regulators and inactivation of complement components

Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato complex differ in their resistance to complement-mediated killing, particularly in regard to human serum. In the present study, we elucidate the serum and complement susceptibility of B. valaisiana, a genospecies with the potential to cause Lyme disease in Europe as well as in Asia. Among the investigated isolates, growth of ZWU3 Ny3 was not affected while growth of VS116 and Bv9 was strongly inhibited in the presence of 50% human serum. Analyzing complement activation, complement components C3, C4 and C6 were deposited on the surface of isolates VS116 and Bv9, and similarly the membrane attack complex was formed on their surface. In contrast, no surface-deposited components and no aberrations in cell morphology were detected for serum-resistant ZWU3 Ny3. While further investigating the protective role of bound complement regulators in mediating complement resistance, we discovered that none of the B. valaisiana isolates analyzed bound complement regulators Factor H, Factor H-like protein 1, C4b binding protein or C1 esterase inhibitor. In addition, B. valaisiana also lacked intrinsic proteolytic activity to degrade complement components C3, C3b, C4, C4b, and C5. Taken together, these findings suggest that certain B. valaisiana isolates differ in their capability to resist complement-mediating killing by human serum. The molecular mechanism utilized by B. valaisiana to inhibit bacteriolysis appears not to involve binding of the key host complement regulators of the alternative, classical, and lectin pathways as already known for serum-resistant Lyme disease or relapsing fever borreliae

Plate-boundary deformation associated with the great Sumatra–Andaman earthquake

The Sumatra–Andaman earthquake of 26 December 2004 is the first giant earthquake (moment magnitude M_w > 9.0) to have occurred since the advent of modern space-based geodesy and broadband seismology. It therefore provides an unprecedented opportunity to investigate the characteristics of one of these enormous and rare events. Here we report estimates of the ground displacement associated with this event, using near-field Global Positioning System (GPS) surveys in northwestern Sumatra combined with in situ and remote observations of the vertical motion of coral reefs. These data show that the earthquake was generated by rupture of the Sunda subduction megathrust over a distance of >1,500 kilometres and a width of <150 kilometres. Megathrust slip exceeded 20 metres offshore northern Sumatra, mostly at depths shallower than 30 kilometres. Comparison of the geodetically and seismically inferred slip distribution indicates that ~30 per cent additional fault slip accrued in the 1.5 months following the 500-second-long seismic rupture. Both seismic and aseismic slip before our re-occupation of GPS sites occurred on the shallow portion of the megathrust, where the large Aceh tsunami originated. Slip tapers off abruptly along strike beneath Simeulue Island at the southeastern edge of the rupture, where the earthquake nucleated and where an M_w = 7.2 earthquake occurred in late 2002. This edge also abuts the northern limit of slip in the 28 March 2005 M_w = 8.7 Nias–Simeulue earthquake

An annotated bibliography of C.J. van der Klaauw with notes on the impact of his work

Van der Klaauw was a professor of Descriptive Zoology in the period 1934–1958. This paper presents a concise annotated overview of his publications. In his work three main topics can be recognized: comparative anatomy of the mammalian auditory region, theoretical studies about ecology and ecological morphology, and vertebrate functional morphology. In particular van der Klaauw developed new concepts on functional morphology, based upon a holistic approach. A series of studies in functional morphology of Vertebrates by his students is added. An overview of recent morphological and theoretical studies show that this new approach had a long lasting impact in studies of functional morphology

Resolving the Sources of Plasma Glucose Excursions following a Glucose Tolerance Test in the Rat with Deuterated Water and [U-13C]Glucose

Sources of plasma glucose excursions (PGE) following a glucose tolerance test enriched with [U-13C]glucose and deuterated water were directly resolved by 13C and 2H Nuclear Magnetic Resonance spectroscopy analysis of plasma glucose and water enrichments in rat. Plasma water 2H-enrichment attained isotopic steady-state within 2–4 minutes following the load. The fraction of PGE derived from endogenous sources was determined from the ratio of plasma glucose position 2 and plasma water 2H-enrichments. The fractional gluconeogenic contributions to PGE were obtained from plasma glucose positions 2 and 5 2H-positional enrichment ratios and load contributions were estimated from plasma [U-13C]glucose enrichments. At 15 minutes, the load contributed 26±5% of PGE while 14±2% originated from gluconeogenesis in healthy control rats. Between 15 and 120 minutes, the load contribution fell whereas the gluconeogenic contribution remained constant. High-fat fed animals had significant higher 120-minute blood glucose (173±6 mg/dL vs. 139±10 mg/dL, p<0.05) and gluconeogenic contributions to PGE (59±5 mg/dL vs. 38±3 mg/dL, p<0.01) relative to standard chow-fed controls. In summary, the endogenous and load components of PGE can be resolved during a glucose tolerance test and these measurements revealed that plasma glucose synthesis via gluconeogenesis remained active during the period immediately following a glucose load. In rats that were placed on high-fat diet, the development of glucose intolerance was associated with a significantly higher gluconeogenic contribution to plasma glucose levels after the load

Female Fertility Affects Men's Linguistic Choices

We examined the influence of female fertility on the likelihood of male participants aligning their choice of syntactic construction with those of female confederates. Men interacted with women throughout their menstrual cycle. On critical trials during the interaction, the confederate described a picture to the participant using particular syntactic constructions. Immediately thereafter, the participant described to the confederate a picture that could be described using either the same construction that was used by the confederate or an alternative form of the construction. Our data show that the likelihood of men choosing the same syntactic structure as the women was inversely related to the women's level of fertility: higher levels of fertility were associated with lower levels of linguistic matching. A follow-up study revealed that female participants do not show this same change in linguistic behavior as a function of changes in their conversation partner's fertility. We interpret these findings in the context of recent data suggesting that non-conforming behavior may be a means of men displaying their fitness as a mate to women

Frequency of extreme Sahelian storms tripled since 1982 in satellite observations

The hydrological cycle is expected to intensify under global warming, with studies reporting more frequent extreme rain events in many regions of the world, and predicting increases in future flood frequency. Such early, predominantly mid-latitude observations are essential because of shortcomings within climate models in their depiction of convective rainfall. A globally important group of intense storms—mesoscale convective systems (MCSs)—poses a particular challenge, because they organize dynamically on spatial scales that cannot be resolved by conventional climate models. Here, we use 35 years of satellite observations from the West African Sahel to reveal a persistent increase in the frequency of the most intense MCSs. Sahelian storms are some of the most powerful on the planet, and rain gauges in this region have recorded a rise in ‘extreme’ daily rainfall totals. We find that intense MCS frequency is only weakly related to the multidecadal recovery of Sahel annual rainfall, but is highly correlated with global land temperatures. Analysis of trends across Africa reveals that MCS intensification is limited to a narrow band south of the Sahara desert. During this period, wet-season Sahelian temperatures have not risen, ruling out the possibility that rainfall has intensified in response to locally warmer conditions. On the other hand, the meridional temperature gradient spanning the Sahel has increased in recent decades, consistent with anthropogenic forcing driving enhanced Saharan warming. We argue that Saharan warming intensifies convection within Sahelian MCSs through increased wind shear and changes to the Saharan air layer. The meridional gradient is projected to strengthen throughout the twenty-first century, suggesting that the Sahel will experience particularly marked increases in extreme rain. The remarkably rapid intensification of Sahelian MCSs since the 1980s sheds new light on the response of organized tropical convection to global warming, and challenges conventional projections made by general circulation models